IQ Survey Results on Current Industry Practices: Part 2-Quantitative Evaluations of Immunogenicity Assessment.

All biotherapeutics have the potential to induce an immunogenic response and generate anti-drug antibodies (ADAs), especially when administered as multiple doses over prolonged periods. However, a clinically meaningful effect of ADAs can be difficult to identify to communicate the impact of immunogenicity on drug exposure, safety and efficacy outcomes in product labels in a way that is useful for health care providers. The immunogenicity working Group, IQ Consortium (Clinical Pharmacology Leadership Group) has conducted a survey to understand the current practices in analyzing immunogenicity data generated during clinical development and its impact on pharmacokinetics, clinically relevant pharmacodynamic biomarkers, safety, and efficacy outcome measures. Information was collected for 93 drugs, spanning multiple drug classes and over the different phases of clinical development, including post-approval. The predominant drug classes reported included monoclonal antibodies or Fc-fusion proteins, endogenous protein replacement therapies, bispecific antibodies, and antibody-drug conjugates. The extent of quantitative evaluation varied and was influenced by several factors, including descriptive analyses, statistical approaches, and modeling. In addition to understanding current practices, this survey also highlights areas for future exploration in analyzing clinical relevance of ADAs which can facilitate the use for regulatory submissions and product labels.